Current pharmacological treatments for smoking cessation, including nicotine replacement therapies and bupropion, are modestly successful in assisting smokers to quit. Moreover, certain barriers limit the success of smoking cessation attempts and even prevent some smokers from attempting to quit, particularly the issue of post-cessation weight gain. A number of ideas have been proposed to explain why weight concerned individuals may have more trouble quitting smoking, including the possibility that attempting to simultaneously control two behaviors, food intake and smoking, leads to failure. However, few laboratory studies have examined the effects of food and tobacco deprivation together, and no pharmacological treatments have been specifically targeted to the concerns of this population. Because current therapies only partially reduce the risk of weight gain and associated concerns, a better understanding of these effects could facilitate the development of more effective treatments for smoking cessation in a weight concerned population. Treatments that attenuate post-cessation weight gain will reduce an important barrier to quitting and motivate smokers who are concerned about this issue to make a quit attempt. In turn, if they are successful, they should accrue important benefits, including reducing their life time exposure to tobacco. In our original grant, we conducted a dose ranging study ofnaltrexone in combination with transdermal nicotine replacement therapy. In this study, we found that low dose naltrexone in combination with the nicotine patch reduced weight gain in those who succeeded in smoking cessation, and improved smoking cessation outcomes in a subset of participants who smoked to control their weight. These findings suggest that low dose naltrexone may provide a novel, highly translatable strategy for addressing the needs of weight concerned smokers. To further investigate these findings, two avenues of investigation are planned: 1) a clinical trial in weight concerned smokers testing the efficacy of low dose naltrexone on weight gain and smoking cessation; and 2) a human laboratory study designed to understand the interactive effects of food and tobacco deprivation on smoking behavior. This study will compare the effects of food deprivation and tobacco deprivation to the effects of tobacco deprivation done on efforts to resist smoking and ad lib smoking.